Morphological and biochemical aspects of central nervous system regeneration will be studied by attacking two principal objectives. The first is concerned with investigating aspects of central and peripheral regeneration to discover mechanisms responsible for the slow, inadequate and apparently uneven regenerative responses seen in the central nervous system after injury; while the second will define the influence of agents selected to promote increased central nervous regeneration. 1. NEUROPLASTICITY STUDIES: (a) Using electronmicroscopy in tandem with fluorescence microscopy, we will compare regeneration in a central adrenergic pathway after lesions at different levels. (b) We will seek to overcome barriers which retard interaction of central and peripheral elements when a peripheral nerve is redirected into the brain. Overcoming these barriers will allow us to document the influence of the CNS microenvironment of regeneration of PNS elements. (c) The morphokinetics of the effector terminal of the small granule-containing cell in the sympathetic nervous system will be explored, as a model for studying the effects of stimulation on an adrenergic nervous terminal. Results of stimulation will be compared with those of the cholinergic terminal documented for Narcine brasiliensis electric organ in these laboratories. 2. PROMOTING CENTRAL NERVOUS REGENERATION: Having set up three model systems we will employ them to determine the role of hypothesized growth-promoting substances in the CNS (e.g., triiodothyronine, concanavalin A, nerve growth factor and cyclic GMP). We will seek to identify agents which stimulate or enhance growth adjacent to a CNS lesion, employing ultrastructural and light microscopic evaluation to determine the magnitude of the regenerative response. BIBLIOGRAPHIC REFERENCE: Chiba, T., B-H. Hwang, T.H. Williams: A method for glyoxylic acid induced fluorescence and ultrastructure of monoamine neurons. Histochemistry, in press, 1976.